The isolation and partial characterization of LAV-2 from two AIDS patients from West Africa was initially described in Clavel et al., C.r. Acad. Sci. (Paris), 302:485-488 (1986) and Clavel et al., Science 233:343 (1986). This virus is related to HIV-1, the causative agent of AIDS, by both its morphology and its biological properties, the latter including its T4+ lymphotropism and its cytopathic effect on T4 cell lines and lymphocytes. However, DNA hybridization studies suggest that there are regions of extensive homology between HIV-1 and LAV-2 particularly in the gag gene, the reverse transcriptase domain in pol, the Q genes, the F gene, and the 3' LTR. The envelope gene, the tat gene, and part of the pol gene seem very divergent. Clavel et al. (ibid.)
Thus, even though HIV-1 and LAV-2 may be related, the heterogeneity in the genes which encode the envelope proteins may explain why serological cross-reactivity between the two species appears to be limited to epitopes of the gag and pol proteins. This may also account for the difficulties of the commercially available HIV-1 screening tests to adequately detect antibodies to LAV-2. Clavel et al. (ibid.) have predicted that, despite the wide divergence between the env genes of HIV-1 and LAV-2, there may exist homologous domains in the envelope glycoproteins of the two viruses which bind them to T4 receptors on the target cells.
It appears that LAV-2 may also be related to a virus known as Simian T-lymphotropic Virus Type 3 ("STLV-3"), a retrovirus first isolated from captive macaques with an AIDS-like disease. Clavel et al. (Nature 324:691-695 (1986)) used radioimmunoprecipitation assays to show that sera from patients infected with LAV-2 reacted with all the STLV-3 proteins, although the proteins of LAV-2 and STLV-3 were distinguishable by differences in molecular weights. The nucleotide sequence of LAV-2 may also be very similar to STLV-3, as LAV-2 probes bound STLV-3 gag and pol regions under stringent conditions, whereas HIV-1 probes did not react with the STLV-3 genome. Southern blots of STLV-3 DNA showed a restriction pattern that was clearly different, however, from LAV-2 DNA.
Another human retrovirus, designated HTLV-IV, has also been isolated from West African patients but has not been associated with an AIDS-like disease. This virus also appears related to STLV-3 and HIV-1 (Kanki et al., Science (1986) 232:238-243). Comparisons of HTLV-IV and LAV-2 have not been reported. Serological evidence for another new retrovirus related to STLV-3 has been reported in residents of West Africa. Barin et al., Lancet, 2:1387-89 (1985).
Hopp and Woods, Proc. Nat. Acad. Sci. USA (1981) 78:3824, describe criteria for selecting peptides as potential epitopes of polypeptides based on their relative hydrophilicity. In one study employing these criteria, a 12-amino acid peptide was synthesized that bound 9% of antibodies elicited by the native protein (Hopp, Molec Immunol. (1981) 18:869). In general Hopp/Woods criteria have not been shown to have a high predictive value, particularly for those regions not associated with the highest peak of hydrophilicity for a particular protein. Furthermore, epitopes have been demonstrated which are not hydrophilic (Kazim et al., Biochem. J. (1982) 203:201). Other studies of polypeptide antigenicity include Green et al., Cell (1982) 28:477, where peptides were employed which elicited antibodies, which antibodies were capable of binding to the native protein, while conversely antibodies which were elicited by the native protein failed to bind to the peptides; and Trainer et al., Nature (1984) 312:127, whose results with myohaemerythrin paralleled those of Green et al.
Synthetic peptides have been generated which immunologically mimic or have been predicted to mimic proteins encoded by HIV-1. See U.S. Pat. No. 4,629,783 and Pat. Publication No. WO 86/06414, which are incorporated herein by reference; NTIS Publication No. PB 86-131562 (U.S. patent application Ser. No. 779,431) and Chang et al., Proc. Natl. Acad. Sci. USA 83:6159-63 (1986). Pauletti et al., Analyt. Biochem. 151:540-546 (1985) used a computer program to predict possible antigenic determinants for the envelope glycoprotein (gp160) of HIV-1. Starcich et al., Cell 45:637-648 (1986) analyzed the entire envelope gene of isolates of HIV-1 and, based on predicted secondary protein structure and hydrophilicity, postulated that certain hypervariable regions represented antigenic sites.